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Open AccessArticle

Lanatoside C Induces G2/M Cell Cycle Arrest and Suppresses Cancer Cell Growth by Attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR Signaling Pathways

1
Department of Genomic Science, School of Biological Sciences, Central University of Kerala, Tejaswini Hills, Periya (P.O) Kasaragod 671316, Kerala, India
2
Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA
3
Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, West Bengal, India
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 792; https://doi.org/10.3390/biom9120792
Received: 21 October 2019 / Revised: 22 November 2019 / Accepted: 22 November 2019 / Published: 27 November 2019
(This article belongs to the Special Issue Antitumor Agents from Natural Sources)
Cardiac glycosides (CGs) are a diverse family of naturally derived compounds having a steroid and glycone moiety in their structures. CG molecules inhibit the α-subunit of ubiquitous transmembrane protein Na+/K+-ATPase and are clinically approved for the treatment of cardiovascular diseases. Recently, the CGs were found to exhibit selective cytotoxic effects against cancer cells, raising interest in their use as anti-cancer molecules. In this current study, we explored the underlying mechanism responsible for the anti-cancer activity of Lanatoside C against breast (MCF-7), lung (A549), and liver (HepG2) cancer cell lines. Using Real-time PCR, western blot, and immunofluorescence studies, we observed that (i) Lanatoside C inhibited cell proliferation and induced apoptosis in cell-specific and dose-dependent manner only in cancer cell lines; (ii) Lanatoside C exerts its anti-cancer activity by arresting the G2/M phase of cell cycle by blocking MAPK/Wnt/PAM signaling pathways; (iii) it induces apoptosis by inducing DNA damage and inhibiting PI3K/AKT/mTOR signaling pathways; and finally, (iv) molecular docking analysis shows significant evidence on the binding sites of Lanatoside C with various key signaling proteins ranging from cell survival to cell death. Our studies provide a novel molecular insight of anti-cancer activities of Lanatoside C in human cancer cells. View Full-Text
Keywords: Cardiac glycosides; Na+/k+-ATPase; G2/M phase; apoptosis; autophagy; molecular docking Cardiac glycosides; Na+/k+-ATPase; G2/M phase; apoptosis; autophagy; molecular docking
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Reddy, D.; Kumavath, R.; Ghosh, P.; Barh, D. Lanatoside C Induces G2/M Cell Cycle Arrest and Suppresses Cancer Cell Growth by Attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR Signaling Pathways. Biomolecules 2019, 9, 792.

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